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In this study, we developed a feeding simulation using the fish schooling behavior model to evaluate growth differences from the feeding spatial distribution. In the proposed simulation, feeding behavior was modeled using the fish schooling model to simulate the amount of feed consumed by each individual. Next, body mass growth was calculated based on the amount of feed consumed. A 3.0-m diameter aquaculture tank was used for the simulation. We used three feeding methods to evaluate how feeding distribution affected growth: Feeding A, B, and C. The feed was distributed in a square pattern with one side length of 1.5, 1.0, or 0.5 m for Feeding A, B, and C groups, respectively. The results revealed that individual differences in body mass resulting from each feeding method differed greatly. The individual difference was largest in the Feeding C group. Here, maximum swimming speed was assumed to be proportional to total length. The feeding area of Feeding C was narrow; therefore, the first individual to arrive in the feeding area dominated the feed. Large individuals accessed the feed more easily than did small individuals. Consequently, the growth of large individuals became more rapid, and the individual differences became large in Feeding C. A rearing test can be conducted in a short time, and the optimal aquaculture operation was easily determined using the proposed simulation method. We concluded that the proposed simulation is useful as a decision-making tool for aquaculture management.

•We demonstrated a significant indirect protective effect of COVID-19 vaccination.•The indirect protective effect of COVID-19 vaccination were attributed to an additive effect together with the direct effect.•These findings emphasize the importance of herd immunity by COVID-19 vaccination for not only unvaccinated but vaccinated individuals. There is little information on relationships between indirect and direct protection by COVID-19 vaccination on close contacts of the vaccinees. Here, we assessed effect modification of direct–indirect action influencing the protective effects of vaccination. Secondary attack rates (SARs) in household contacts (n = 2422) depending on vaccination status of the index cases (n = 1112) with known vaccination history during the delta variant-dominant period (August 2–November 2, 2021) in two public health jurisdictions were calculated using multivariable logistic regression analysis to assess indirect protection by COVID-19 vaccination as adjusted odds ratios (aORs) for SARs. The impact of the time of index case vaccination on indirect-direct protective effects was also assessed. Contacts of index cases receiving 2× COVID-19 vaccinations showed significantly lower SARs than contacts of unvaccinated index cases (aOR:0.48, 95 %CI = 0.32–0.74). Relative to contacts where neither index cases nor contacts themselves were vaccinated (0,0), those with (2,0), (0,2) and (2,2) had lower SARs (0.45, 95 %CI = 0.24–0.82, 0.24, 95 %CI = 0.17-0.032, 0.11, 95 %CI = 0.06–0.20, respectively. No significant interactions on the SARs regarding times of vaccination between index cases and household contacts were observed, indicating additive but not synergistic protection. The indirect protective effects of COVID-19 vaccination were attributed to an additive effect together with the direct effect on onward transmission in the household setting. These findings emphasize the importance of herd immunity by COVID-19 vaccination not only for unvaccinated but also vaccinated individuals.

The bitter taste of drugs is an important impediment to medication adherence for pediatric patients. To develop a formulation that can be easily taken by pediatric patients, we prepared film-coated molded tablets to mask their bitterness and investigated their properties. We manufactured 5 and 3 mm film-coated tablets, which were easy for children to swallow. The tablets also exhibited rapid disintegration (≤30 s), making them suitable for tube administration. The formulation of the film-coating layer was experimentally optimized. Tablets (measuring 5 and 3 mm thick) containing the model drug dextromethorphan hydrobromide were film-coated by weight of the uncoated tablets (4% by weight). These tablets rapidly disintegrated and masked the bitterness for 10 s. An examination of the coated tablets revealed that the film covered the periphery, which may mask the bitterness. The findings demonstrate that coating small molded tablets with a film enables the manufacture of tablets that could be more tolerable for pediatric patients and suitable for tube administration.

Aquaculture is increasingly important for meeting the rising global demand for seafood. To improve the sustainability of the aquaculture industry, there have been increasing efforts to develop smart aquaculture technologies, including simulation methods, to optimize growth and feeding strategies. This study developed a simulation model, which incorporates a fish behavior model based on the Boids model and a dynamic energy budget, for the purpose of improving the efficiency of rainbow trout ( Oncorhynchus mykiss ) aquaculture. The proposed simulation method predicts the growth trajectories of individual fish and evaluates the effects of different feeding levels on fish growth and feed efficiency. The simulation results were compared with those of a live rearing experiment to evaluate its accuracy. Rainbow trout growth trajectories were accurately predicted. However, longer-term simulations showed increasing divergence between the simulated and experimental data. The proposed simulation method allows the optimization of growth and feeding efficiency under various feeding strategies. Further refinements of the simulation model, including considering density effects and parameter adjustments, may lead to more accurate long-term predictions. The simulation-based approach developed in this study will contribute to a better understanding of rainbow trout growth, with potential applications for other aquaculture species and contexts.

Exosomes are extracellular vesicles released by various cell types and play roles in cell–cell communication. Several studies indicate that cancer cell‐derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell‐derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the effect of cancer‐cell derived exosomes on tumor growth by analyzing their biodistribution. Murine melanoma B16BL6‐derived exosomes increased the proliferation and inhibited the apoptosis of B16BL6 cells, which was associated with an increase and decrease in the levels of proliferation‐ and apoptosis‐related proteins, respectively. GW4869‐induced inhibition of exosome secretion decreased the proliferation of B16BL6 cells, and treatment of GW4869‐treated cells with B16BL6‐derived exosomes restored their proliferation. Next, we treated B16BL6 tumors in mice with B16BL6‐derived exosomes and examined the biodistribution and cellular uptake of these exosomes. After the intratumoral injection of radiolabeled B16BL6‐derived exosomes, most radioactivity was detected within the tumor tissues of mice. Fractionation of cells present in the tumor tissue showed that fluorescently labeled exosomes were mainly taken up by B16BL6 cells. Moreover, intratumoral injection of B16BL6‐derived exosomes promoted tumor growth, whereas intratumoral injection of GW4869 suppressed tumor growth. These results indicate that B16BL6 cells secrete and take up their own exosomes to induce their proliferation and inhibit their apoptosis, which promotes tumor progression. Biodistribution and cellular uptake of cancer cell‐derived exosomes were analyzed. Cancer cells efficiently take up their own exosomes to induce tumor progression. Inhibition of exosomes secretion suppressed tumor growth.

Background Interference with activities of daily living can negatively impact maternal practices both physically and psychologically. This study aimed to explore the patterns of interference with activities of daily living and perineal pain among Japanese women until 1 month postpartum. Furthermore, we aimed to describe how both perineal pain and delivery-related factors were associated with interference with activities of daily living. Methods This study was part of a larger prospective longitudinal study conducted at five maternity hospitals in Japan. The participants were 293 women who had full-term vaginal deliveries and singleton infants. Participants self-evaluated their perineal pain and interference with activities of daily living using a 100 mm visual analogue scale and ‘behaviour that interferes with daily life scale’ at day 1, day 5, and 1 month postpartum. We used a linear mixed model to calculate the fixed-effects parameter estimates and their 95% confidence intervals. Interference with activities of daily living, which included difficulty sitting, difficulty moving, and difficulties with excretion and cleanliness, were set as the dependent variables. Results The final analysis included 184 participants with a mean age of 31.5±4.5 years. Perineal pain and the three sub-scales of interference with activities of daily living reduced from day 1 to 5 postpartum, and further from day 5 to 1 month postpartum (perineal pain, p <0.01, p <0.01; difficulty sitting, p <0.01, p <0.01; difficulty moving, p <0.01, p <0.01; difficulties with excretion and cleanliness, p <0.01, p <0.01). These tendencies did not change, even adjusted for independent variables using a mixed model. In the mixed model for follow-up data, perineal pain was a significantly and positively associated with three sub-scales of interference with activities of daily living, even after adjusted for perineal injury and episiotomy. Conclusions Positive relationships were observed between perineal pain and interference with activities of daily living until 1 month postpartum, although both reduced. To promote maternal role attainment through child-rearing since early postpartum, midwives should pay additional attention to mothers’ perineal pain as it could negatively affect their daily life and child-rearing.

Few studies have assessed incubation periods of the severe acute respiratory syndrome coronavirus 2 Delta variant. This study aimed to elucidate the transmission dynamics, especially the incubation period, for the Delta variant compared with non-Delta strains. We studied unvaccinated coronavirus disease 2019 patients with definite single exposure date from August 2020 to September 2021 in Japan. The incubation periods were calculated and compared by Mann–Whitney U test for Delta (with L452R mutation) and non-Delta cases. We estimated mean and percentiles of incubation period by fitting parametric distribution to data in the Bayesian statistical framework. We enrolled 214 patients (121 Delta and 103 non-Delta cases) with one specific date of exposure to the virus. The mean incubation period was 3.7 days and 4.9 days for Delta and non-Delta cases, respectively (p-value = 0.000). When lognormal distributions were fitted, the estimated mean incubation periods were 3.7 (95% credible interval (CI) 3.4–4.0) and 5.0 (95% CI 4.5–5.6) days for Delta and non-Delta cases, respectively. The estimated 97.5th percentile of incubation period was 6.9 (95% CI 5.9–8.0) days and 10.4 (95% CI 8.6–12.7) days for Delta and non–Delta cases, respectively. Unvaccinated Delta variant cases had shorter incubation periods than non–Delta variant cases.

Applying Artificial Intelligence (AI) to the monitoring of live fish in natural environments represents a promising approach to the sustainable management of aquatic resources. Detecting and counting fish in water through video analysis is crucial for fish population statistics. This study employs AI algorithms, specifically YOLOv10 (You Only Look Once version 10) for identifying the presence fish in video frames, combined with the DeepSORT (Deep Simple Online and Realtime Tracking) algorithm to count the number of fish individual moving across the frames. A total of 9,002 frames were extracted from 13 videos recorded in five different environments: areas with submerged tree roots, shallow marine regions, coral reefs, bleached coral reefs and seagrass meadows. To train the recognition model, the dataset was divided into training, validation and testing sets in 8:1:1 ratio. The results demonstrated that the model achieved an accuracy of 89.5%, with processing times of 6.2ms for preprocessing, 387.0ms for inference and 0.9ms for postprocessing per image. The combination of YOLO and DeepSORT enhances the accuracy of tracking objects in aquatic environments, showing great potential for the monitoring of fishery resources.

Guanosine- and uridine-rich single-stranded RNA (GU-rich RNA) is an agonist of Toll-like receptor (TLR) 7 and TLR8 and induces strong immune responses. A nanostructured GU-rich RNA/DNA assembly prepared using DNA nanotechnology can be used as an adjuvant capable of improving the biological stability of RNA and promoting efficient RNA delivery to target immune cells. To achieve a sustained supply of GU-rich RNA to immune cells, we developed a GU-rich RNA/DNA hydrogel (RDgel) using nanostructured GU-rich RNA/DNA assembly, from which GU-rich RNA can be released in a sustained manner. A hexapod-like GU-rich RNA/DNA nanostructure, or hexapodRD6, was designed using a 20-mer phosphorothioate-stabilized GU-rich RNA and six phosphodiester DNAs. Two sets of hexapodRD6 were mixed to obtain RDgel. Under serum-containing conditions, GU-rich RNA was gradually released from the RDgel. Fluorescently labeled GU-rich RNA was efficiently taken up by DC2.4 murine dendritic cells and induced a high level of tumor necrosis factor-α release from these cells when it was incorporated into RDgel. These results indicate that the RDgel constructed using DNA nanotechnology can be a useful adjuvant in cancer therapy with sustained RNA release and high immunostimulatory activity.

Previous studies using B16BL6-derived exosomes labelled with gLuc-lactadherin (gLuc-LA), a fusion protein of Gaussia luciferase (a reporter protein) and lactadherin (an exosome-tropic protein), showed that the exosomes quickly disappeared from the systemic circulation after intravenous injection in mice. In the present study, the mechanism of rapid clearance of intravenously injected B16BL6 exosomes was investigated. gLuc-LA-labelled exosomes were obtained from supernatant of B16BL6 cells after transfection with a plasmid DNA encoding gLuc-LA. Labelling was stable when the exosomes were incubated in serum. By using B16BL6 exosomes labelled with PKH26, a lipophilic fluorescent dye, it was demonstrated that PKH26-labelled B16BL6 exosomes were taken up by macrophages in the liver and spleen but not in the lung, while PKH26-labelled exosomes were taken up by the endothelial cells in the lung. Subsequently, gLuc-LA-labelled B16BL6 exosomes were injected into macrophage-depleted mice prepared by injection with clodronate-containing liposomes. The clearance of the intravenously injected B16BL6 exosomes from the blood circulation was much slower in macrophage-depleted mice than that in untreated mice. These results indicate that macrophages play important roles in the clearance of intravenously injected B16BL6 exosomes from the systemic circulation.